6-29667540-C-T

Variant names:

• chr6-29667540-C-T
• rs2071652
• NM_206809.4:c.551-103C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206809.4(MOG):​c.551-103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 1,181,212 control chromosomes in the GnomAD database, including 2,031 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.046 (207 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1824 hom.)
• Consequence: MOG NM_206809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253
• Publications: 5 publications found

Genes affected

MOG (HGNC:7197): (myelin oligodendrocyte glycoprotein) The product of this gene is a membrane protein expressed on the oligodendrocyte cell surface and the outermost surface of myelin sheaths. Due to this localization, it is a primary target antigen involved in immune-mediated demyelination. This protein may be involved in completion and maintenance of the myelin sheath and in cell-cell communication. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

MOG Gene-Disease associations (from GenCC):

• narcolepsy 7

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOG	NM_206809.4	c.551-103C>T		intron_variant	Intron 3 of 7	ENST00000376917.8	NP_996532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOG	ENST00000376917.8	c.551-103C>T		intron_variant	Intron 3 of 7	1	NM_206809.4	ENSP00000366115.3

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 6979 AN: 152036 Hom.: 207 Cov.: 32

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0953

Gnomad FIN AF: 0.0307

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0354

Gnomad OTH AF: 0.0484

GnomAD4 exome AF: 0.0464 AC: 47723 AN: 1029058 Hom.: 1824 AF XY: 0.0486 AC XY: 25830 AN XY: 531416

African (AFR) AF: 0.0529 AC: 1304 AN: 24642

American (AMR) AF: 0.0299 AC: 1281 AN: 42902

Ashkenazi Jewish (ASJ) AF: 0.0503 AC: 1170 AN: 23246

East Asian (EAS) AF: 0.185 AC: 6978 AN: 37630

South Asian (SAS) AF: 0.0968 AC: 7497 AN: 77420

European-Finnish (FIN) AF: 0.0278 AC: 1467 AN: 52736

Middle Eastern (MID) AF: 0.0980 AC: 479 AN: 4888

European-Non Finnish (NFE) AF: 0.0354 AC: 25509 AN: 719904

Other (OTH) AF: 0.0446 AC: 2038 AN: 45690

GnomAD4 genome AF: 0.0458 AC: 6976 AN: 152154 Hom.: 207 Cov.: 32 AF XY: 0.0459 AC XY: 3416 AN XY: 74378

African (AFR) AF: 0.0560 AC: 2323 AN: 41514

American (AMR) AF: 0.0325 AC: 497 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3472

East Asian (EAS) AF: 0.120 AC: 622 AN: 5168

South Asian (SAS) AF: 0.0954 AC: 458 AN: 4802

European-Finnish (FIN) AF: 0.0307 AC: 326 AN: 10616

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0354 AC: 2409 AN: 67994

Other (OTH) AF: 0.0479 AC: 101 AN: 2108

Alfa AF: 0.0407 Hom.: 368

Bravo AF: 0.0457

Asia WGS AF: 0.0870 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.7
DANN	Benign	0.80
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2071652; hg19: chr6-29635317; COSMIC: COSV65306732; COSMIC: COSV65306732;